INJECTOR WITH FLUID SUPPLY AND MOBILE-PHASE DISPOSAL
Patent Information
- Application Number
- DE502018015526
- Authority / Receiving Office
- DE · DE
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2017-10-30
- Filing Date
- 2018-10-26
- Publication Date
- 2025-02-13
- Estimated Expiration
- 2038-10-26
AI Technical Summary
Conventional injectors for sample separation devices in HPLC systems often cause pressure and flow fluctuations during sample injection, leading to undesirable artifacts in chromatographic separation results.
An injector design that includes a discharge device to remove a predetermined amount of mobile phase from the main flow path and a supply device to introduce a corresponding amount of fluidic sample or solvent, ensuring that the amounts removed and supplied at least partially compensate each other, thereby maintaining a constant flow and pressure during sample injection.
This design effectively suppresses flow and pressure fluctuations, ensuring trouble-free sample separation by maintaining a constant flow rate and pressure, thus improving the accuracy and reliability of chromatographic separation.
Description
TECHNICAL BACKGROUND
[0001] The present invention relates to an injector for injecting a fluidic sample containing material to be analyzed into a mobile phase in a main flow path of a sample separation device, a sample separation device and a method.
[0002] In HPLC, a liquid (mobile phase) is typically moved through a stationary phase (e.g., a chromatographic column) at a very precisely controlled flow rate (for example, in the range of microliters to milliliters per minute) and at high pressure (typically 20 to 1000 bar and above, currently up to 2000 bar), at which the compressibility of the liquid is noticeable, in order to separate individual components of a sample liquid introduced into the mobile phase. Such an HPLC system is known, for example, from EP 0,309,596 B1 of the same applicant, Agilent Technologies, Inc.
[0003] Liquid chromatography requires the introduction of a fluidic sample into the system. Systems for introducing (also referred to as injecting or introducing) a fluidic sample are disclosed in US 4,939,943, US 3,916,692, US 3,376,694, and US 6,893,569.
[0004] Unlike conventional injectors, a principle known as "feed injection" maintains a continuous flow path between a fluid drive and a sample separation device, for example, when a fluidic sample is introduced at a fluidic T-point. Examples of injectors based on the "feed injection" principle are described in US 2015 / 0316516 A1 and US 2015 / 0226710 A1.
[0005] However, the process of introducing the fluidic sample into the flow path between the fluid drive and the sample separation device according to the "feed injection" principle can lead to artifacts, such as fluctuations or jumps in pressure and flow rate. This can undesirably affect the chromatographic separation result. US Patent 2004 / 0251203 A1 discloses a liquid chromatograph in which no buffer solution is added to the solvent. Instead, this buffer solution is added to the mobile phase during operation before being fed to an injector. REVELATION
[0006] It is an object of the invention to provide an injector for a sample separation device that enables sample separation essentially free from pressure and / or flow fluctuations caused by sample injection. This object is achieved by means of the independent claims. Further embodiments are shown in the dependent claims.
[0007] According to the present invention, an injector (which may also be referred to as a sample injection device) is provided for injecting a fluidic sample into a mobile phase in a sample separation device (for example, a chromatographic sample separation device), wherein the injector provides a main flow path between a fluid drive (for example, a high-pressure pump) and a sample separation device (for example, a chromatographic separation device), wherein the fluid drive is configured for driving the mobile phase and the sample separation device for separating the fluidic sample injected into the mobile phase, and a discharge device (in particular configured in addition to and / or separately from the main flow path) for removing a (in particular predetermined) quantity of the mobile phase from the main flow path (and in particular into a discharge flow path, which may also be generally referred to as a discharge path).and a feed device (in particular designed in addition to and / or separately from the main flow path) for feeding a (in particular predetermined) quantity of the fluidic sample and / or a solvent (in particular from a feed flow path, which can also generally be referred to as a feed path) into the main flow path, wherein the quantity discharged and the quantity supplied (preferably being supplied and discharged essentially simultaneously and) at least partially compensate each other.
[0008] The discharge device can be located at least partially within a discharge flow path, which may be fluidically coupled to the main flow path via at least one discharge coupling point (also called a branch point), but otherwise run externally to the main flow path. Similarly, the feed device can be located at least partially within a feed flow path, which may be fluidically coupled to the main flow path via at least one feed coupling point (also called a junction point), but otherwise run externally to the main flow path. Preferably, the at least one discharge coupling point can be located upstream of the at least one feed coupling point within the main flow path. The discharge flow path and the feed flow path can optionally be fluidically coupled to each other, preferably at ends opposite to the discharge coupling point and the feed coupling point, respectively.The discharge flow path and the supply flow path can be operatively coupled, in particular such that the fluid flows in the discharge flow path and the supply flow path correspond to each other, preferably in terms of timing and / or magnitude, i.e., for example, that a flow rate in the discharge flow path corresponds to a flow rate in the supply flow path in terms of timing and / or magnitude, and preferably these are equal. Preferably, the coupling between the discharge flow path and the supply flow path can be designed such that there is no (fluidic) flow between the discharge flow path and the supply flow path, i.e., that no fluid is transferred from the discharge flow path to the supply flow path.
[0009] According to one embodiment, a sample separation device is provided for separating a fluidic sample, wherein the sample separation device comprises a fluid drive for driving a mobile phase, a sample separation device for separating the fluidic sample in the mobile phase, and an injector with the features described above for injecting the fluidic sample into the mobile phase.
[0010] A method is also provided in which a mobile phase is driven in a main flow path of a sample separation device between a fluid drive and a sample separation unit, a (particularly predetermined) quantity of the mobile phase is removed from the main flow path (particularly at a discharge flow path branching off from the main flow path at a fluidic bifurcation point and being separately formed from the main flow path), and a (particularly predetermined) quantity of a fluidic sample and / or a solvent is fed into the main flow path (particularly at a feed flow path entering the main flow path at a fluidic junction point and being separately formed from the main flow path), wherein the quantity removed and the quantity fed are dimensioned such that they at least partially compensate each other.
[0011] In the context of this application, the term "fluidic sample" is understood to mean in particular a medium containing gas and / or a liquid as well as the matter to be analyzed (for example, a biological sample such as a protein solution, a pharmaceutical sample, etc.).
[0012] Within the scope of the present applications, the term "mobile phase" is understood to mean, in particular, a fluid (especially a gas and / or a liquid) that serves as a carrier medium for transporting the fluidic sample from the fluid drive to the sample separation device. For example, the mobile phase can be a solvent (e.g., organic and / or inorganic) or a solvent composition (e.g., water and ethanol).
[0013] In the context of these applications, the term "solvent" is understood to mean, in particular, a fluid (for example, organic and / or inorganic) (furthermore, in particular, a gas and / or a liquid) used in separation analysis. For example, the solvent may be a diluent for the fluidic sample or a rinsing solution. The solvent may also be a solvent composition (for example, water and ethanol).
[0014] Within the scope of this application, the term "main flow path" (which can also be referred to more generally as flow path) can be understood to mean, in particular, a fluidic path for transporting a fluid from the fluid drive (in particular a high-pressure pump) to the sample separation device (in particular a chromatography column). Preferably, other fluidic paths of the injector or the sample separation device do not belong to the main flow path. In particular, fluidic paths of the injector or the sample separation device that branch off from and / or enter the main flow path cannot be considered part of the main flow path. In particular, a discharge flow path branching off from the main flow path, in which at least part of a discharge device separate from the main flow path may be implemented, can be designed as a fluidic path separate from and distinct from the main flow path.Alternatively or additionally, a feeder flow path leading into the main flow path, in which at least part of a feeder device separate from the main flow path may be implemented, can be designed as a fluidic path separate from and different from the main flow path.
[0015] In the context of these applications, the term "at least partially compensate" is understood to mean, in particular, that the discharged quantity reduces the supplied quantity, or the total quantity or fill quantity, either wholly or partially, so that ultimately no additional fluid quantity (in the sense of complete compensation) or a reduced additional fluid quantity compared to the supplied quantity flows towards the sample separation device. This compensation can also occur in such a way that the discharged quantity even exceeds the supplied quantity.
[0016] According to the invention, when injecting a fluidic sample into a separation path between a fluid drive and a sample separation device, a fluidic sample (or a solvent) intended for separation can be introduced, and mobile phase can be removed from the main flow path to reduce artifacts resulting from the altered flow in the main flow path. Significant changes in flow rate or pressure, or the formation of other artifacts (such as fluidic oscillations, fluctuations, or pressure surges), which can conventionally occur when injecting a fluidic sample, for example, using the "feed injection" principle, can be significantly suppressed or completely eliminated by fully or at least partially compensating for the amount of fluid introduced into the main flow path during injection by removing mobile phase.To illustrate, during sample injection, the flow towards the sample separation device can be kept essentially constant, and thus the pressure (especially at the sample separation device) can be kept essentially constant. This means that the flow is only marginally disturbed during sample injection. By suppressing artifacts resulting from the injection process, trouble-free sample separation can be ensured.
[0017] Further embodiments of the injector, the sample separation device and the method are described below.
[0018] According to one embodiment, the main flow path (in particular a high-pressure path) need not contain either the discharge device or the supply device. In particular, a fluidic discharge flow path may be provided that leads away from the main flow path (for example, at a fluidic branch point). Alternatively or additionally, a fluidic supply flow path may be provided that can merge into the main flow path (for example, at a fluidic junction point). The latter can occur, in particular, while the flow in the main flow path (especially under high pressure) is maintained. Furthermore, the discharge flow path and the supply flow path may not be identical to the main flow path in relation to it, nor may they form part of the main flow path, but rather be separate or independent of it (but preferably fluidly coupled to the main flow path continuously or temporarily).However, the main flow path, the feed flow path and the discharge flow path can be controlled and synchronized together.
[0019] According to one embodiment, no fluid (in particular a liquid) flows through the discharge flow path and the supply flow path. Instead, according to this embodiment, fluid discharged from the discharge flow path is not introduced into the supply flow path. The fluids flowing in the supply flow path and the discharge flow path can therefore be different from each other.
[0020] According to one embodiment, a predetermined or defined quantity of the fluidic sample can be fed into the main flow path. This allows for a particularly precise balance between the added and removed fluid. For example, it is possible to feed the fluidic sample continuously and thus without interruption until the fluidic sample in a corresponding sample reservoir (for example, a sample intake volume, such as a so-called "sample loop") is depleted. However, it is also possible to introduce a specific sample volume into the main flow path in a discontinuous process with one or more interruptions, for example, defined by the distance traveled by a piston in a piston pump within a piston chamber.
[0021] According to one embodiment, the respective quantity can be a volume. In other words, at least partial compensation can be achieved by partially or completely offsetting a volume of supplied fluidic sample or solvent with a volume of removed solvent or mobile phase. Alternatively, based on a mass of sample or solvent supplied, the added fluid quantity can also be fully or partially compensated by removing a corresponding mass of mobile phase.
[0022] According to one embodiment, the feed and discharge devices can be configured such that the quantity fed (in particular, a volume of fluid fed) and the quantity discharged (in particular, a volume of fluid discharged) differ from each other by less than 30 percent by volume, and in particular by less than 10 percent by volume. Correspondingly small discrepancies between the quantities of fluid fed and discharged can be compensated for by the sample separation device without significantly impairing the accuracy of the measurement or causing pronounced artifacts. Furthermore, a permissible discrepancy can be defined in relation to the system flow rate, for example, such that the discrepancy divided by the injection duration (which yields the deviation of the total flow rate) is less than 30 percent, and in particular less than 10 percent, of the system flow rate.
[0023] According to one embodiment, the feed and discharge devices can be configured such that the quantity supplied (in particular, a supplied fluid volume) and the quantity discharged (in particular, a discharged fluid volume) are essentially equal. Thus, the diverted quantity can at least substantially correspond to the quantity supplied. It is preferred that the quantity supplied and the discharged fluid are completely identical (and especially preferably also identical with respect to flow rate, although modifications to the flow rate are also possible). With an essentially complete or exact compensation of the quantities of supplied and discharged fluid, particularly robust operation of the sample separation device is enabled.
[0024] According to one embodiment, the flow rate of the discharged mobile phase can correspond to the flow rate of the supplied fluidic sample and / or solvent. In this context, flow rate is understood to mean, in particular, the volume of a flowing fluid per unit time. Preferably, the feed and discharge devices can be configured to carry out the supply of the fluidic sample and / or solvent and the discharge of the mobile phase in such a way that the overall flow rate in the main flow path outside the section between the feed and discharge devices remains unchanged or substantially unchanged.In other words, the feed and discharge devices can advantageously be configured to carry out the feed of the fluidic sample and / or solvent and the discharge of the mobile phase such that the flow rate downstream of the feed device and the flow rate upstream of the discharge device are equivalent, and in particular, substantially equal. With substantially complete flow rate compensation, artifacts can be particularly well suppressed or eliminated.
[0025] According to one embodiment, the feed and discharge devices can be configured to synchronize the feed of the fluidic sample and / or solvent and the discharge of the mobile phase, i.e., to coordinate the timing of the feed and discharge processes. For example, a common control unit can establish a well-defined temporal and thus functional relationship between the feed of a fluidic sample or solvent on the one hand and the discharge of a mobile phase on the other. In this way, the temporal relationship between the fed and discharged fluids can be coordinated so that fluidic artifacts such as pressure fluctuations or pressure surges can be suppressed particularly effectively. A mechanical coupling of the feed and discharge devices is also possible.Receiving devices (or pumps) for supplying and removing the respective fluid can support such synchronization, for example by subjecting the pistons to a fixed phase relationship as a result of the mechanical coupling.
[0026] According to one embodiment, the feed and discharge devices can be configured to perform the feed of the fluidic sample and / or solvent and the discharge of the mobile phase simultaneously. Particularly good interference resistance, artifact suppression, and performance can be achieved if the time interval for feeding the fluidic sample and / or solvent into the main flow path and the time interval for removing the mobile phase from the main flow path are identical or at least overlap in time.
[0027] According to one embodiment, the injector can have a fluidic junction in the main flow path where the supplied fluidic sample and / or solvent, on the one hand, and the mobile phase driven by the fluid actuator (and not previously discharged), on the other hand, are combined as fluidic flows during supply. At such a fluidic junction, the partial flows of the mobile phase conveyed between the fluid actuator and the sample separation device, on the one hand, and the fluidic sample or solvent injected into the main flow path, on the other, can combine to form a common flow that is conveyed by the fluid actuator to the sample separation device. Such a fluidic junction can, for example, be configured as a fluidic T-piece, a fluidic Y-piece, or a fluidic X-piece.
[0028] According to one embodiment, the injector can have a fluidic branch point in the main flow path, at which the mobile phase, driven by the fluid actuator, is at least partially discharged from the main flow path. In particular, at the branch point, the mobile phase can be partially directed towards the sample separation device and partially discharged from the main flow path. Such a fluidic branch point can, for example, be configured as a fluidic T-piece, a fluidic Y-piece, or a fluidic X-piece. However, a branch point can also be located outside the injector.
[0029] According to one embodiment, the fluidic branch point can be arranged upstream of the fluidic junction. The mobile phase conveyed to the sample separation device by the fluid drive then initially flows to the fluidic branch point, where it can split into two partial flows. One of the partial flows can then continue to the fluidic junction. In particular, the fluidic branch point and the fluidic junction can be arranged relative to each other such that the fluid does not bypass the branch point after passing through the junction.
[0030] According to one embodiment, the main flow path can be coupled between the fluid drive and the sample separation device in such a way that a flow between the fluid drive and the sample separation device is maintained continuously during operation of the sample separation device. Advantageously, an interruption of the flow during the injection of the fluidic sample or solvent and / or during the partial decoupling of mobile phase from the main flow path can be avoided with an injector according to the described embodiment of the invention, since the flow of mobile phase between the fluid drive and the sample separation device continues even during injection. This measure further reduces the causes that can conventionally lead to the formation of fluidic artifacts during the operation of the sample separation device.
[0031] According to one embodiment, the discharge device can be purely passive, featuring a restrictor (i.e., a fluidic resistance) that can be switched on or off. Advantageously, this restrictor can be configured such that an input flow is essentially equal to a passively discharged flow. In this configuration, the discharge device is not actively controlled by a pump or similar device, but can be activated simply by connecting a fluidic restrictor to the main flow path. The magnitude of the restrictor's fluidic resistance then determines which subset of the mobile phase is discharged from the main flow path.
[0032] According to one embodiment, the injector can have at least one pump, in particular a piston pump, whose piston(s) is or are movable for supplying the fluidic sample and / or the solvent and / or for removing the mobile phase. For the purposes of this application, a "piston pump" is understood to be, in particular, a fluid actuator comprising at least one piston that reciprocates in at least one associated piston chamber and pumps fluid during reciprocating. With one or more piston pumps, the supplied and discharged fluid quantities can be precisely and efficiently coordinated.
[0033] However, as an alternative to implementing at least one piston pump, it is possible to provide one or preferably at least two pumping devices (for example, peristaltic pumps) that are not designed as piston pumps. For example, such pumping devices can also be electrically synchronized and thereby accomplish the described supply and discharge. Therefore, pumps other than piston pumps are also possible for driving the fluids (for example, peristaltic pumps). Further embodiments are described below (see in particular the following four paragraphs) using the example of piston pumps, whereby a person skilled in the art will understand that for all the following embodiments, one, two, or more pumps of other types can also be used instead of one, two, or more piston pumps.
[0034] According to one embodiment, a common piston pump can be provided for supplying the fluidic sample and / or solvent and for removing the mobile phase, and can be configured to simultaneously supply the fluidic sample and / or solvent and remove the mobile phase in a push-pull operation. Such an embodiment is described in Figure 3As illustrated, a piston pump with two variable fluid intake volumes can be operated such that a piston movement changes the two variable fluid intake volumes depending on the current piston position. One fluid intake volume can then contain the fluidic sample or solvent, while the other can contain the mobile phase. Each piston movement increases one fluid intake volume at the expense of the other, and vice versa. In this way, a particularly compact and simple injector can be created.
[0035] According to another embodiment, the injector can have a first piston pump for supplying the fluidic sample and / or solvent and a second piston pump for removing the mobile phase. An injector with two synchronized piston pumps, one for removing the mobile phase and the other for supplying the fluidic sample or solvent, is particularly precise and offers greater flexibility. This configuration allows for a significant increase in the reliability of separation results.
[0036] According to one embodiment, the first piston pump and the second piston pump can be operatively coupled, and in particular synchronized. This can be achieved, for example, by means of an eccentric disk that can be coupled on the drive side to the reciprocating pistons of the two piston pumps in such a way that the, for example, cyclic piston strokes of the two piston pumps can be precisely correlated. In other words, the two piston pumps can then be operated with a fixed phase relationship.
[0037] According to one embodiment, the at least one piston pump can be designed to operate continuously for any number of piston cycles. This enables continuous operation of the injector, thus avoiding inactive periods. In other words, a continuously running pump can be provided in the circulation path. An associated sample separation device can therefore be operated particularly efficiently.
[0038] According to one embodiment, the feeding device can include a fluid valve that can be switched to feed the fluidic sample from a sample source and / or to feed the solvent into the main flow path. For example, such a fluid valve can have a rotor component and a stator component that can be rotated relative to each other and can have corresponding fluidic structures. For example, fluidic channels (for example, in the form of grooves) can be formed in the rotor component that can be fluidically coupled to or decoupled from fluidic connections (for example, referred to as ports) of the stator component in order to set different fluidic coupling states according to different valve states.
[0039] According to one embodiment, the injector may only have a single fluid valve (see, for example, Figure 7In other words, the injector can be equipped with a single fluid valve. This allows the injector and the associated sample separation device to be designed in a particularly compact manner.
[0040] According to one embodiment, the injector can have a fluidically coupled sample intake volume (which can also be referred to as a "sample loop") connected to the fluid valve, wherein the fluid valve is switchable such that, after the fluidic sample has been drawn from the sample source into the sample intake volume by switching the fluid valve, the fluidic sample drawn into the sample intake volume can be fed to the main flow path. In this way, the amount of fluidic sample to be supplied can be set very precisely (for example, corresponding to the size of the sample intake volume).
[0041] According to one embodiment, the injector can have a pre-compression device configured to pre-compress the fluidic sample and / or the solvent before it is introduced into the main flow path. This advantageously avoids or at least significantly suppresses undesirable pressure surges when a fluid valve is switched. If, before the fluidic sample is introduced into the main flow path, its pressure is brought close to or even exactly to the pressure in the main flow path, undesirable pressure surges that could impair the reliability of the system can be mitigated or completely avoided.
[0042] According to one embodiment, the pre-compression device can be configured to pre-compress the sample receiving volume before it is switched to the main flow path. The fluidic sample or solvent can then first be applied to the sample receiving volume or sample loop, followed by an increase in the pressure of the sample receiving volume to match the pressure in the main flow path, and finally, the fluidic sample or solvent can be introduced into the main flow path in a pre-compressed state, thus avoiding a significant pressure surge. Furthermore, this can increase the service life of the sample separation device and other system components, as damaging pressure surges are reduced or completely avoided.
[0043] According to one embodiment, the pre-compression device can include a piston pump that can be operated for pre-compression and for supplying the fluidic sample and / or solvent to the main flow path. Visually, by moving the piston of the piston pump, the pressure of the fluidic sample or solvent can be increased to such an extent that the pressure difference between the original pressure of the fluidic sample or solvent on the one hand and the main flow path on the other is advantageously reduced. In another operating state of the injector, the same piston pump can be used to pump the fluidic sample and / or solvent.
[0044] According to one embodiment, the fluid valve can be configured to form or integrate at least part of the main flow path, the feed device, and / or the discharge device within its interior. Integrating one or more of these components into the injector's fluid valve enables a particularly compact configuration, short fluidic paths, and therefore low dead volumes and a reduction or complete elimination of the unflushed main flow path sections.
[0045] According to one embodiment, the solvent supplied by the feed device can be at least partially the mobile phase removed by the discharge device (in particular, a mobile phase generated during one of the previous injection processes or during the current injection process). In this way, the amount of operating fluids required for the operation of the injector or the sample separation device, as well as the amount of liquid waste, can be reduced.
[0046] According to one embodiment, the discharge device can be coupled downstream of the feed device, in particular such that complete mixing of the mobile phase flow with the supplied solvent and / or fluidic sample flow can occur before a mixed flow reaches a branch point. This can be used, in particular, in combination with at least partial reuse of the discharged mobile phase (or liquid) for controlled dilution of the sample. Furthermore, this embodiment can be advantageous in process analysis or in a two-dimensional liquid chromatography (2D-LC) apparatus, in particular in a tandem LC apparatus as described in application WO 2012 / 175111 A1 of the same applicant.This allows, for example, a representative sample to be introduced onto the separation apparatus without overloading the apparatus or bringing it into contact with an undiluted or insufficiently diluted sample matrix. The fact that a proportional portion of the sample is discarded during injection is usually acceptable or even advantageous in applications of this type.
[0047] According to one embodiment, the sample separation device can be a preparative sample separation device. In a preparative sample separation device (for example, a preparative HPLC), large fluid volumes are moved (for example, up to 500 ml for sample analysis), and the flow rate can be, for example, up to 20 ml / min or more. The sample volumes can also range from several milliliters to several hundred milliliters and beyond. Alternatively, according to an exemplary embodiment, a sample separation device can also be designed as an analytical sample separation device, which operates with significantly lower fluid volumes and flow rates.
[0048] The sample separation device can be a microfluidic instrument, a life science instrument, a liquid chromatograph, an HPLC (high-performance liquid chromatograph), an UHPLC system, an SFC (supercritical liquid chromatograph), a gas chromatograph, an electrochromatograph, and / or a gel electrophoresis instrument. However, many other applications are possible.
[0049] The fluid drive or fluid pump can, for example, be designed to transport the mobile phase through the system at high pressure, for example several hundred bar up to 1000 bar and more.
[0050] The sample separation device may include a sample injector or sample delivery unit for introducing the sample into the fluidic separation path. Such a sample injector may have an injection needle that can be coupled to a seat within a corresponding fluid path, and the needle can be extended from this seat to receive the sample. After reinserting the needle into the seat, the sample can be further processed.
[0051] The sample separation device may include a fraction collector for collecting the separated components. Such a fraction collector can, for example, direct the different components into separate liquid containers. Alternatively, the analyzed sample can be discharged into a waste container.
[0052] Preferably, the sample separation device can include a detector for detecting the separated components. Such a detector can generate a signal that can be observed and / or recorded, and which is indicative of the presence and quantity of the sample components in the fluid flowing through the system. BRIEF DESCRIPTION OF THE FIGURES
[0053] Other objectives and many of the accompanying advantages of exemplary embodiments of the present invention will become readily apparent and more readily understood with reference to the following more detailed description of exemplary embodiments in conjunction with the accompanying drawings. Features that are essentially or functionally the same or similar are designated with the same reference numerals. Figure 1 Figure 1 shows a sample separation device designed as an HPLC measuring instrument according to an exemplary embodiment of the invention. Figure 2shows an injector for a sample separation device according to an exemplary embodiment of the invention. Figure 3 shows an injector for a sample separation device according to another exemplary embodiment of the invention. Figure 4A and Figure 4B show an injector for a sample separation device according to yet another exemplary embodiment of the invention, wherein Figure 4A a supply of a fluidic sample from a sample intake volume and Figure 4B This corresponds to drawing a fluidic sample into a sample receiving volume. Figure 5 shows an injector for a sample separation device according to an exemplary embodiment of the invention. Figure 6 shows an injector for a sample separation device according to another exemplary embodiment of the invention. Figure 7 shows an injector for a sample separation device according to an exemplary embodiment of the invention. Figure 8shows an injector for a sample separation device according to yet another exemplary embodiment of the invention. Figure 9 shows an injector for a sample separation device according to an exemplary embodiment of the invention. Figure 10 shows an injector for a sample separation device according to an exemplary embodiment of the invention. Figure 11 shows the injector according to Figure 10 in a different switching state of the fluid valve shown. Figure 12 shows the injector according to Figure 10 in yet another switching state of the fluid valve shown. Figure 13 shows an injector for a sample separation device according to a further exemplary embodiment of the invention. Figure 14 shows an injector for a sample separation device according to yet another exemplary embodiment of the invention. Figure 15 shows an injector for a sample separation device according to another exemplary embodiment of the invention.
[0054] The representation in the drawing is schematic.
[0055] Before exemplary embodiments of the invention are described in more detail with reference to the figures, some basic considerations of the present invention, on the basis of which exemplary embodiments of the invention have been developed, should be described in general terms.
[0056] According to the present invention, an injector for a sample separation device is provided, which can be operated (preferably, but not necessarily, according to the "feed injection" principle) to remove mobile phase from the system when a fluidic sample or solvent is introduced into a main flow path, thereby increasing the reliability of the separation result. This counteracts an excessive increase in flow when introducing the fluidic sample or solvent. In this way, it is particularly possible to introduce a fluidic sample into a main flow path without significantly disturbing the fluidic flow in the main flow path outside the injector (where the injector can include the inlet and outlet points). This advantageously suppresses undesirable flow or pressure fluctuations and pressure surges.
[0057] It is possible to inject a fluidic sample into the separation path without reducing, stopping, changing the value of, or otherwise manipulating the flow rate provided by a fluid drive for propelling the mobile phase. In particular, this avoids disrupting the continuous operation of the fluid drive, affecting a programmed gradient shape, eliminating the need for control coupling with the fluid drive, and / or offering other advantages. To achieve this, for example, a corresponding portion of the mobile phase can be removed from the main flow path simultaneously or synchronously with the injection of the fluidic sample or solvent into the main flow path.The amount of fluid removed (especially the volume of fluid removed) can be selected to be essentially equal to the amount of fluidic sample introduced, thereby eliminating disturbances and / or transition phenomena in the overall flow or pressure. For example, the removal flow rate can be set to be essentially equal to the injection flow rate. The removal flow rate or volume can correspond to the volume of the removed compressed fluid (especially a liquid).
[0058] According to one embodiment, the removed mobile phase can be reintroduced into the main flow path at a different time and / or position, at which point the fluid drive flow rate can be readjusted. It is also possible to return the removed mobile phase to a mobile phase source reservoir or to a waste path. Furthermore, it is possible to at least partially recover the energy of the discharge flow to drive the injection flow.
[0059] The discharge position for removing the mobile phase (in particular a solvent or solvent composition) can be located upstream or downstream of the feed position for supplying the fluidic sample or solvent. The discharge position can also be located in the vicinity of the feed position, but preferably at a sufficient distance from it to avoid interfering with the feeding and discharge process through fluidic interaction phenomena. It is also possible to arrange the discharge position in a fluidic side path or parallel path relative to the feed position. For example, the discharge position can be located at any desired position between a high-pressure outlet of one of several channels of the fluid drive and an inlet of the sample separation device (in particular a chromatographic column).In particular, it is possible to return the mobile phase to the corresponding mobile phase source vessel if it has been discharged from one of the channels of a multi-channel pump, for example a high-pressure mixing binary pump (i.e., before the mixing point).
[0060] It is also possible (for example, in a fluid drive designed as a multi-channel gradient pump with high-pressure capability and mixing functionality) to position the discharge point in a region of the flowing mobile phase where it is a strong solvent, or in a region where it is a weak solvent. This allows the composition of the mobile phase to be further adjusted or modulated in a section related to the supplied sample or solvent volume.
[0061] The discharged flow can be actively discharged, for example, using an associated pump. Alternatively, it is also possible to generate the discharged flow passively (for example, by passively branching a flow, where the discharge flow rate is determined by the fluidic restriction of the discharge flow path).
[0062] Advantageously, a sample feed flow path can be provided that includes a metering pump (for example, a piston pump), a sample receiving volume, a movable needle, and a seat for fluid-tight needle retention. Preferably, such a sample feed flow path can be flushed separately. The use of a corresponding embodiment provides a hydraulic injection function with the ability to compress or decompress the sample receiving volume, needle and seat, and metering pump before or after connection to the main flow path. In one embodiment, the metering pump can also be flushed with fresh solvent to prevent carryover.
[0063] Both fluidic pathways (e.g., needle, sample intake volume, seat, and metering pump on the one hand, and analytical pump as fluid drive and chromatographic column as sample separation device on the other) can be operated independently of each other, except during the injection of the fluidic sample or solvent. Therefore, it is advantageous to select different solvents for each fluidic pathway as needed. The removal of the mobile phase, preferably performed during the introduction of the fluidic sample or solvent, allows disturbances in the fluidic system to be reduced to almost zero during the introduction of the sample or solvent.
[0064] According to one embodiment, a fluidic sample can be introduced immediately or instantaneously (especially without pressure increase) according to the "feed injection" principle. Continuous introduction of the fluidic sample is also possible by allowing the sample to flow into the main flow path to reduce its solvent concentration and then focusing it at the sample separation device (especially a column). A reduction in concentration is possible, but this can advantageously be achieved without reducing the sample volume. Mixing with the mobile phase can be performed to minimize its influence on the separation. Introducing larger quantities of the fluidic sample is also possible.It is possible to introduce the fluidic sample over a long time interval, whereby the sample flows into the main flow path to reduce the solvent strength of the sample and, according to the embodiment, is diluted with the mobile phase and focused at the sample separation device (in particular a column).
[0065] According to one embodiment, the speed of the "feed injection" can be adjusted depending on the requirements of a (especially chromatographic) separation method.
[0066] According to one embodiment, it is also advantageously possible to draw the fluidic sample into a sample receiving volume in a direction opposite to the direction along which the sample is injected into the main flow path. This reduces undesirable dispersion effects.
[0067] To implement an injector according to an exemplary embodiment, it may be sufficient to implement only a high-pressure fluid valve, which can preferably be designed as a rotor valve with a rotor component and a stator component.
[0068] It is particularly preferred to pre-compress the fluidic sample or solvent to be injected, for example using a metering pump, before establishing the fluidic connection to the main flow path. Preferably, this is done with the same apparatus that drew up the sample (alternatively, it is also possible to provide an additional apparatus for this purpose). According to one embodiment, the sample can in any case be necessarily compressed before it is injected.
[0069] The removal of the mobile phase and the injection of the fluidic sample or solvent can advantageously be carried out using a single pump, which may have coupled pistons. An embodiment with coupled pistons can advantageously be operated with near-zero force as soon as the two piston chambers are subjected to the same pressure conditions. It is also possible to provide a single piston in a single piston pump, which can be operated in a push-pull configuration using at least two separate pump chambers. Alternatively, the coordinated operation of several different pumps is also possible.
[0070] The fluidic sample can be introduced into a sample intake volume of the injector by implementing the injector with a needle-seat configuration. Alternatively, a sample container can also be directly coupled fluidically to the injector.
[0071] Regardless of the solvents used in the main analytical flow path, the fluidic sample can be introduced with only a marginal influence from the solvent used to dilute it. Therefore, it is particularly possible to introduce the fluidic sample even in the presence of a strong sample solvent.
[0072] Exemplary embodiments offer significant advantages: The described injector configuration allows a sample path (for example, comprising a needle, seat, and sample intake volume) to be excluded from the main flow path with the fluid drive and sample separation device. The injection speed is adjustable and can be implemented, in particular, as a method parameter.
[0073] A further advantage of exemplary embodiments is that the sample can be focused depending on the flow rate of a metering pump. Furthermore, the injected volume can be varied independently of the discharged volume. The sample path can be designed to be pre-compressible. By pre-compressing the sample path, pressure fluctuations due to the injection process can be reduced to almost zero. The injector architecture according to exemplary embodiments can be implemented with or without a needle architecture. It is also possible to perform multiple sample injections with a single intake of fluidic sample (especially according to the "feed injection" principle). Injections at short intervals are also possible (for example, to monitor a reaction, such as a chemical or biological one). Such a reaction can, for example, take place in a sample receiving volume.A fluid obtained as a result of such a reaction can be introduced, in whole or in part, into the main flow path between the fluid drive and the sample separation device. If a flushing function is implemented, as described above, unwanted sample carryover can be suppressed particularly effectively. Furthermore, the injection volume is essentially freely and infinitely adjustable, depending on the size of the sample receiving volume.
[0074] Figure 1 Figure 1 shows an HPLC system as an example of a sample separation device 10 with a control device 70 coupled thereto according to an exemplary embodiment of the invention.
[0075] Figure 1Figure 1 shows the basic structure of an HPLC system as an example of a measuring instrument designed as a sample separation device 10, such as can be used for liquid chromatography. A fluid pump, acting as a fluid drive 20 and supplied with solvents from a supply unit 25, drives a mobile phase through a sample separation device 30 (such as a chromatographic column), which contains a stationary phase. A degasser 27 can degas the solvents before they are fed to the fluid drive 20. A sample introduction unit, also referred to as an injector 40, which has a switchable fluid valve 90, is arranged between the fluid pump 20 and the separation device 30 to introduce a sample liquid into the fluidic separation path. The stationary phase of the sample separation device 30 is appropriately selected and designed to separate components of the sample.A detector 50 with a flow cell detects separated components of the sample, and a fractionation device can be provided to discharge separated components of the sample into designated containers. Unneeded liquids can be discharged into a drain container 60.
[0076] The control device 70 controls the individual components 20, 25, 27, 30, 40, 50, 60 of the sample separation device 10.
[0077] As already mentioned, the injector 40 serves to inject a fluidic sample into a mobile phase. A main flow path 100 of the injector 40 is arranged between the fluid drive 20 and the sample separation device 30 and, according to an exemplary embodiment of the invention, must never be interrupted during operation. The fluid drive 20 serves to drive the mobile phase. The sample separation device 30 functions to separate the fluidic sample injected into the mobile phase.
[0078] One in Figure 1The schematically depicted discharge device 104 of the injector 40 is configured to divert a quantity (for example, a specific volume) of the mobile phase from the main flow path 100. In the illustrated embodiment, the diverted mobile phase is fed to a waste port 131. A schematically depicted feed device 102 of the injector 40 is designed to feed a quantity (for example, a specific volume) of the fluidic sample into the main flow path 100 simultaneously with the discharge of the predetermined quantity of the mobile phase from the main flow path 100. The control device 70 synchronizes or controls the feed device 102 and the discharge device 104, as well as the fluid valve 90, preferably such that the diverted volume of the mobile phase corresponds exactly to the supplied volume of the fluidic sample.This allows any additional flow in the main flow path 100 resulting from the injection of the fluidic sample by the discharged mobile phase to be precisely compensated or balanced. If the flow rate of the discharged mobile phase corresponds to the flow rate of the supplied fluidic sample, the flow rate in the main flow path 100 remains unchanged when the fluidic sample is injected into the main flow path 100 outside the injector 40. In this way, it is possible to significantly suppress or even completely avoid pressure jumps, pressure oscillations, and other artifacts resulting from the fluidic sample injection process. A chromatographic separation result can then be obtained with high accuracy and freedom from interference.As an alternative to the described complete compensation of the supplied fluid volume by the discharged fluid volume, only partial compensation of the supplied fluid volume by the discharged fluid volume can also be achieved (which can be described as undercompensation or overcompensation and can also be used to at least partially suppress the described artifacts).
[0079] Figure 2 Figure 1 shows an injector 40 for a sample separation device 10 according to an exemplary embodiment of the invention. In this embodiment, the flow rate remains constant for a portion of the main flow path 100 outside the section between reference numerals 108 and 106.
[0080] The injector 40 according to Figure 2 exhibits a fluidic branch point 108, designed here as a fluidic T-point, in the main flow path 100. Mobile phase, driven by the fluid drive 20 according to Figure 2The fluid, which is conveyed from left to right, is partially directed towards the sample separation device 30 at branch point 108, while the remainder is diverted from the main flow path 100. Thus, at fluidic branch point 108, the fluidic flow of the mobile phase splits into two separate partial flows.
[0081] In the case of injector 40 according to Figure 2 Furthermore, a fluidic junction 106, also designed as a fluidic T-point, is provided in the main flow path 100. At the fluidic junction 106, the supplied fluidic sample on the one hand and the mobile phase not discharged from the main flow path 100 at the fluidic branch point 108 on the other hand are combined as fluidic partial flows into a common flow, which flows to the sample separation device 30.
[0082] Figure 2Figure 110 also shows that a first piston pump 110 is provided for supplying the fluidic sample to the main flow path 100 and a second piston pump 112 is provided for removing the mobile phase from the main flow path 100. Reference numeral 189 is shown in Figure 112. Figure 2A mechanical coupling between the first piston pump 110 and the second piston pump 112 is shown. The quantity and speed of the supply and discharge of the respective fluid are set by the speed of movement of the respective piston of the first piston pump 110 and the second piston pump 112, respectively. For this purpose, the control unit 70 controls both piston pumps 110 and 112 to ensure synchronized operation. In other words, the first piston pump 110 and the second piston pump 112 are operatively coupled to each other by virtue of the common control by the control unit 70 in such a way that their piston movements are coordinated. The current directions of movement of the respective pistons (corresponding to an injection process) of the first piston pump 110 and the second piston pump 112 are shown in Figure 2 represented by arrows 133 and 135.
[0083] As in Figure 2As shown, in this embodiment, the main flow path 100 between the fluid drive 20 and the sample separation device 30 is fluidically coupled in such a way that the flow between the fluid drive 20 and the sample separation device 30 is maintained continuously during operation of the sample separation device 10, even during the introduction of the fluidic sample from a feed flow path 187 (which, for example, partially contains the feed device 102) into the main flow path 100 and during the discharge of a portion of the mobile phase from the main flow path 100 into a discharge flow path 185 (which, for example, partially contains the discharge device 104). A flow rate that is not only continuous but preferably also constant is achieved by the defined discharge of a portion of the mobile phase from the main flow path 100, the volume of which preferably corresponds exactly to the volume of the supplied fluidic sample.
[0084] Figure 3shows an injector 40 for a sample separation device 10 according to another exemplary embodiment of the invention.
[0085] Figure 3 Figure 1 shows a sample intake volume 120, which can also be referred to as a "sample loop", and which can be used to take up a predetermined amount of the fluidic sample. The embodiment shown in Figure 1 is a sample intake volume 120, which can also be referred to as a "sample loop" and which can be used to take up a predetermined amount of the fluidic sample. Figure 3 differs from that according to Figure 2 especially also because injector 40 according to Figure 3Only a single piston pump 110 is provided, which both supplies the fluidic sample to the main flow path 100 and discharges the mobile phase from the main flow path 100. The single piston pump 110 has a movable piston 114, the position of which in a piston chamber 139 defines the partial volumes occupied by a piston chamber section 137 on one side of the piston 114 and another piston chamber section 141 on the opposite side of the piston 114. The sum of the partial volumes of piston chamber section 137 and the other piston chamber section 141 is always constant. Piston chamber section 137 serves to receive diverted mobile phase, and the other piston chamber section 141 serves to receive incoming fluidic sample. The piston 114 can be moved in a defined manner, controlled by the control device 70. Figure 3As the piston 114 moves from left to right, it draws mobile phase from the fluidic branching point 108 into the piston chamber section 137 and simultaneously pushes fluidic sample from the other piston chamber section 141 or from the sample receiving volume 120 towards the fluidic junction 106. Thus, according to Figure 3 The common piston pump 110 is provided and configured for supplying the fluidic sample and removing the mobile phase in a push-pull operation, simultaneously supplying the fluidic sample and removing the mobile phase. The injector 40 according to Figure 3 It can therefore be designed to be particularly compact and also be easy to operate in terms of control technology.
[0086] Optional and in Figure 3 non-return valves not shown (see reference 145 in Figure 4A and Figure 4B) in the fluid lines in the pump head, which connect the fluidic branch point 108 with the piston pump 110 and the piston pump 110 with the fluidic junction point 106, can be implemented to ensure a one-way fluidic flow and prevent unwanted flow in the opposite direction. Furthermore, it is possible to design the piston chamber 139 as a two-part unit, such that part of the single common piston 114 is at least partially exposed between the two sub-chambers (see reference numerals 137, 141).
[0087] Figure 4A and Figure 4B Figure 1 shows an injector 40 for a sample separation device 10 according to another exemplary embodiment of the invention. A fluidic sample can be drawn from a container (not shown) (see reference numeral 118 in Figure 1). Figure 7 ). Figure 4A corresponds to the supply of a fluidic sample from a sample intake volume (see reference numeral 120 in Figure 7 ). Figure 4BThis corresponds to drawing a fluidic sample into a sample receiving volume. Figure 4B Figure 131 shows a waste connection. The two piston pumps 110, 112 shown are designed to be continuously operable without interruption over any number of piston cycles.
[0088] In Figure 4A and Figure 4B The figure shows that the two pistons 114 of the two piston pumps 110, 112 are operatively coupled by means of a coupling element 143 (for example an eccentric disc) such that the movement of the pistons 114 has a fixed phase relationship to each other. Figure 4A and Figure 4B The figures show various check valves 145, which determine the flow direction of the various fluids.
[0089] In Figure 4A and Figure 4B The discharged flow is denoted by V-, whereas the supplied flow is denoted by V+. Preferably, the injector 40 is used according to Figure 4A and Figure 4BThe system is operated in such a way that the relationship |V - | = |V + | holds true, since the supplied flow is then exactly compensated by the discharged flow, and the injection of the fluidic sample into the main flow path 100 can therefore be carried out in a flow-neutral manner. The volumes of the piston chambers of the piston pumps 110, 112, as well as the strokes of the pistons 114 of the piston pumps 110, can be set identically to satisfy the aforementioned relationship.
[0090] It should be mentioned that in the exemplary embodiments of Figure 2 to Figure 4B (in particular Figure 3 and Figure 4A and Figure 4BIt is possible to perform a slow movement of the piston(s) before injecting the sample to reduce the partial volume of the piston chamber section 141 or the volume in the cylinder of the piston pump 110 for the purpose of pre-compression of the sample. This results in a partial volume (compression volume) of the mobile phase being withdrawn from the path of the piston pump 110 without compensation, but the disturbance remains very small because the withdrawal occurs only slowly (in contrast to a sudden activation and sudden compression of the sample).
[0091] Figure 5 Figure 1 shows an injector 40 for a sample separation device 10 according to an exemplary embodiment of the invention. The operating state according to Figure 2 is shown. Figure 5 refers to the hydraulic connections during the introduction of a fluidic sample into the main flow path 100.
[0092] According to Figure 5The injector 40 has a rotary fluid valve 90. The fluid valve 90 is composed of a stationary stator component and a rotating rotor component. The stator component has ports 147 as fluidic connections. In addition, the stator component also has a static fluid line 149, which in the illustrated embodiment is designed as a groove. Several rotatable and thus switchable fluid lines 151 of the rotor component are shown in Figure 5 Only one is shown; the others are, for example, in Figure 7 shown. The fluid valve 90 shown integrates within its interior, among other things, a part of the main flow path 100 in the form of the static flow line 149 designed as a groove.
[0093] In a fluidic path that includes the Figure 5The check valve 145' shown contains a fluidic restriction R2. A spring preload of the check valve 145' determines the fluid pressure at which the mobile phase can flow through the path with the fluidic restriction R2. In other words, the check valve 145' is intended to prevent passive flow when a force is applied below an adjustable threshold. An alternative implementation of the check valve 145' as a spring-loaded check valve is, for example, the implementation of an active switch. The static fluid line 149 has a different fluidic restriction R1, where, according to Figure 5The relationship is: R2 >> R1. This means that a large portion of the mobile phase supplied by the fluid drive 20 flows through the static fluid line 149 and from there along the main flow path 100 to the sample separation device 30, whereas only a smaller portion of this mobile phase flows through the restriction R2 to the piston pump 110. In other words, the mobile phase at reference numeral 177 is divided between the two fluidic paths according to the values of the hydraulic resistances R1 and R2. The portion of the mobile phase flowing through the fluidic restriction R2 is the one referred to by Figure 1 to Figure 4B described removed mobile phase to at least partially compensate for the supplied fluidic sample, which can be supplied at reference numeral 179.
[0094] Figure 6 shows an injector 40 for a sample separation device 10 according to another exemplary embodiment of the invention.
[0095] In this embodiment, the mobile phase to be removed is not drained or introduced by means of the piston pump 110, but is merely passively diverted into a fluidic path 153 with a specific fluidic restriction R2 and discharged via a waste port 131.
[0096] Figure 7 shows an injector 40 for a sample separation device 10 according to an exemplary embodiment of the invention.
[0097] The fluid valve 90 according to Figure 7 The injector 40 can be switched from a sample source 118 into the main flow path 100 to supply the fluidic sample. Furthermore, the injector 40 has, according to Figure 7A sample intake volume 120 ("sample loop") is fluidically coupled to the fluid valve 90 via two ports 147. For example, the sample intake volume 120 can hold a fluid with a volume in the range between 10 ml and 500 ml. The fluid valve 90 can be switched such that, after the fluidic sample has been drawn from the sample source 118 into the sample intake volume 120, the fluidic sample held in the sample intake volume 120 is fed to the main flow path 100 by switching the fluid valve 90. A conditioning fluid 155 (for example, a diluent or a rinsing solution) is provided in a corresponding liquid container 157 and fluidically coupled to a port 147 of the fluid valve 90.
[0098] Furthermore, the injector 40 exhibits according to Figure 7Advantageously, a pre-compression device 122 is used, which is configured to pre-compress the sample intake volume 120 before switching to the main flow path 100. According to Figure 7 The pre-compression device 122 is implemented by means of a correspondingly controlled piston pump 110, which can be operated to pre-compress the sample receiving volume 120 and to supply the fluidic sample to the main flow path 100.
[0099] To introduce fluidic sample into the main flow path 100, the fluid valve 90 can be switched such that the single fluid line 151, designed as a radial groove, is rotated 180° relative to the valve position according to Figure 7 The fluidic sample then flows from the sample source 118 through a port 147 and this radial groove via a central port 147 into the sample receiving volume 120. Afterwards, the fluid valve is inserted into the Figure 7The valve circuit shown is switched. The fluidic sample now contained in the sample receiving volume 120 is pumped by means of the piston pump 110 to the port 147 in the center of the fluid valve 90 and passes through the radial groove and the junction 106 designed as port 147 into the main flow path 100, where the fluidic sample, together with the mobile phase, is conveyed by means of the fluid drive 20 to the sample separation device 30.
[0100] Figure 8 shows an injector 40 for a sample separation device 10 according to another exemplary embodiment of the invention.
[0101] The exemplary embodiment according to Figure 8 differs from the embodiment according to Figure 7 in particular by the fact that according to Figure 8The fluidic sample is introduced from the sample container 118 into the sample receiving volume 120 by extending a movable needle 159 (see reference numeral 181) from a seat 161 and immersing it in the sample container 118 to receive the sample. The fluidic sample can then be drawn into the sample receiving volume 120 by means of the piston pump 110. Subsequently, the needle 159 is retracted back into the seat 161.
[0102] Figure 9 Figure 1 shows an injector 40 for a sample separation device 10 according to an exemplary embodiment of the invention. The embodiment according to Figure 9 is similar to the one according to Figure 8 , but uses a different fluid valve 90.
[0103] Figure 10, Figure 11 and Figure 12Figure 1 shows an injector 40 for a sample separation device 10 according to an exemplary embodiment of the invention in different switching states of the associated fluid valve 90. Reference numeral 163 denotes a purge port, which is optional, as are waste ports 131. It is possible to use the injector 40 in a dual "push-pull" operation according to an exemplary embodiment. Figure 10 to Figure 12 An inner area of the fluid valve 90 is designed as a switchable connection, which is connected in the manner shown. Curved lines in Figure 10 to Figure 12 represent jumper connections. Figure 10 The illustration depicts the extraction and injection of a fluid. Figure 11 refers to rinsing and ejection. In Figure 12 This shows a compression.
[0104] Figure 13, Figure 14 and Figure 15 Figure 1 shows an injector 40 for a sample separation device 10 according to an exemplary embodiment of the invention. Figure 13 to Figure 15It is shown that injectors 40 can be designed with very different valve configurations according to exemplary embodiments of the invention.
[0105] It should be noted that the term "have" does not exclude other elements and that "a" does not exclude a plurality. Elements described in connection with different embodiments may also be combined. It should also be noted that reference numerals in the claims should not be interpreted as limiting the scope of protection of the claims.
Claims
1. An injector (40) for injecting a fluidic sample containing matter to be analyzed into a mobile phase in a sample separation apparatus (10), the injector (40) comprising: a main flow path (100) between a fluid drive (20) and a sample separation device (30), the fluid drive (20) being configured to drive the mobile phase and the sample separation device (30) being configured to separate the fluidic sample injected into the mobile phase; a discharge device (104) for discharging an amount of the mobile phase from the main flow path (100); a supply device (102) for supplying an amount of the fluidic sample and / or a solvent into the main flow path (100); wherein the discharged amount and the supplied amount at least partially compensate each other.
2. The injector (40) according to claim 1, wherein a flow rate of the discharged mobile phase corresponds to a flow rate of the supplied fluidic sample and / or the supplied solvent.
3. The injector (40) according to claim 1 or 2, wherein the discharge device (104) is configured passively with a connectable restrictor (r2).
4. The injector (40) according to one of claims 1 to 3, comprising a fluidic combining point (106) in the main flow path (100), at which the supplied fluidic sample and / or the supplied solvent on the one hand and the mobile phase driven by means of the fluid drive (20) on the other hand are combined as fluidic flows during supply.
5. The injector (40) according to one of claims 1 to 4, comprising a fluidic branching point (108) in the main flow path (100), at which the mobile phase is at least partially discharged from the main flow path (100), preferably at which the mobile phase driven by means of the fluid drive (20) is partially guided in the direction of the sample separation device (30) and is partially discharged from the main flow path (100).
6. The injector (40) according to claim 5, wherein the fluidic branching point (108) is arranged upstream of the fluidic combining point (106).
7. The injector (40) according to one of claims 1 to 6, comprising at least one pump (110, 112) for supplying the fluidic sample and / or the solvent and / or for discharging the mobile phase, preferably at least one piston pump (110, 112), the piston (114) of which is movable for supplying the fluidic sample and / or the solvent and / or for discharging the mobile phase.
8. The injector (40) according to claim 7, wherein a common pump (110), preferably a common piston pump (110), is provided for supplying the fluidic sample and / or the solvent and for discharging the mobile phase and is configured to simultaneously effect the supply of the fluidic sample and / or the solvent and the discharge of the mobile phase.
9. The injector (40) according to claim 7 or 8, comprising a first pump (110) for supplying the fluidic sample and / or the solvent and a second pump (112) for discharging the mobile phase, wherein preferably the first pump (110) and the second pump (112) are operatively coupled to each other, preferably synchronized with each other.
10. The injector (40) according to one of claims 1 to 9, wherein the supply device (102) comprises a fluid valve (90) which is switchable for supplying the fluidic sample from a sample source (118) and / or for supplying the solvent into the main flow path (100).
11. The injector (40) according to claim 10, comprising a sample receiving volume (120) fluidically coupled to the fluid valve (90), wherein the fluid valve (90) is switchable such that after receiving the fluidic sample from the sample source (118) into the sample receiving volume (120) by switching the fluid valve (90), the fluidic sample received in the sample receiving volume (120) can be supplied to the main flow path (100).
12. The injector (40) according to one of claims 1 to 11, comprising a precompressing device (122) which is configured to pre-compress the fluidic sample and / or the solvent before supplying into the main flow path (100).
13. A sample separation apparatus (10) for separating a fluidic sample, the sample separation apparatus (10) comprising: a fluid drive (20) for driving a mobile phase; a sample separation device (30) for separating the fluidic sample in the mobile phase; and an injector (40) according to one of claims 1 to 12 for injecting the fluidic sample into the mobile phase.
14. The sample separation apparatus (10) according to claim 13, wherein the sample separation device (30) is configured as a chromatographic separation device, preferably as a chromatographic separation column.
15. A method comprising: driving a mobile phase, which is provided for injection of a fluidic sample containing matter to be analyzed, in a main flow path (100) of a sample separation apparatus (10) between a fluid drive (20) and a sample separation device (30); discharging an amount of the mobile phase from the main flow path (100); supplying an amount of a fluidic sample and / or a solvent into the main flow path (100); wherein the discharged amount and the supplied amount are dimensioned such that they at least partially compensate each other.